Neoadjuvant Therapy Regimens for Hilar Cholangiocarcinoma Before Liver Transplant.

OBJECTIVES: Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA. METHODS: A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method. RESULTS: Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines. CONCLUSIONS: These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.

Use of the Toxicity Index in Evaluating Adverse Events in Anal Cancer Trials: Analysis of RTOG 9811 and RTOG 0529.

Novel toxicity metrics that account for all adverse event (AE) grades and the frequency of may enhance toxicity reporting in clinical trials. The Toxicity Index (TI) accounts for all AE grades and frequencies for categories of interest. We evaluate the feasibility of using the TI methodology in 2 prospective anal cancer trials and to evaluate whether more conformal radiation (using Intensity Modulated Radiation Therapy) results in improved toxicity as measured by the TI. Patients enrolled on NRG/RTOG 0529 or nonconformal RT enrolled on the 5-Fluorouracil/Mitomycin arm of NRG/RTOG 9811 were compared using the TI. Patients treated on NRG/RTOG 0529 had lower median TI compared with patients treated with nonconformal RT on NRG/RTOG 9811 for combined GI/GU/Heme/Derm events (3.935 vs 3.996, P=0.014). The TI methodology is a feasible method to assess all AEs of interest and may be useful as a composite metric for future efforts aimed at treatment de-escalation or escalation.

Is There a Benefit to Adjuvant Chemotherapy in Resected, Early Stage Pancreatic Ductal Adenocarcinoma?

BACKGROUND: The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease. METHODS: The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality. RESULTS: Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months, p < 0.01). Subset analyses based on individual "good" prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months, p < 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months, p = 0.19) and those with all "good" prognostic features (95.9 months vs 90.6 months, p = 0.15), AC was not associated with improved survival. CONCLUSIONS: In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC.

Systemic Therapy for Resected Pancreatic Adenocarcinoma: How Much is Enough?

BACKGROUND: Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even if they do, the impact of reduced dose density (DD) on survival is not known. PATIENTS AND METHODS: A single institutional prospective database was queried for patients with PDAC who underwent curative resection between 2009 and 2018. The primary outcome was DD, defined as the percentage of total planned chemotherapy actually received and associated survival. RESULTS: Of the 126 patients included, 38.9% underwent a neoadjuvant approach, which was associated with a greater median number of completed chemotherapy cycles (5 cycles versus 4 cycles, p < 0.01) and a higher median total DD (93.0% versus 65.0%, p < 0.01), compared with an adjuvant treatment approach. In both groups, adjuvant chemotherapy completion rates were low, with only 55 patients completing all adjuvant cycles. After sequential survival analysis, patients who received a DD ≥ 80% had improved median overall survival (OS) (27.1 months versus 18.6 months, p = 0.01), compared with patients who achieved a DD < 80%. On multivariate Cox proportional-hazards modeling, only the presence of lymphovascular invasion (HR: 1.77, 95% CI: 1.04-2.99, p = 0.04) and DD < 80% (HR: 1.91, 95% CI: 1.23-3.00, p = 0.01) were associated with decreased OS. CONCLUSIONS: In this cohort study, patients who received ≥ 80% DD had significantly better OS. DD should be considered an important prognostic metric in pancreatic cancer, and strategies are needed to improve chemotherapy tolerance to improve patient outcomes.

Radiation therapy in borderline resectable pancreatic cancer: A review.

BACKGROUND: Borderline resectable pancreatic cancer constitutes a complex clinical entity, presenting the clinician with a locally aggressive disease that has a proclivity for distant spread. The benefits of radiation therapy, such as improved local control and improved survival, have been questioned. In this review we seek to summarize the existing evidence on radiation therapy in borderline resectable pancreatic cancer and highlight future areas of research. METHODS: A comprehensive review of PubMed for clinical studies reporting outcomes in borderline resectable pancreatic cancer was performed in June 2021, with an emphasis placed on prospective studies. RESULTS: Radiologic "downstaging" in borderline resectable pancreatic cancer is a rare event, although some evidence shows increased clinical response to neoadjuvant chemotherapy over radiation therapy. Margin status seems to be equivalent between regimens that use neoadjuvant chemotherapy alone and regimens that include neoadjuvant radiation therapy. Local control in borderline resectable pancreatic cancer is likely improved with radiation therapy; however, the benefit of improved local control in a disease marked by systemic failure has been questioned. Although some studies have shown improved survival with radiation therapy, differences in the delivery and tolerance of chemotherapy between the neoadjuvant and adjuvant setting confound these results. When the evidence is evaluated as a whole, there is no clear survival benefit of radiation therapy in borderline resectable pancreatic cancer. CONCLUSION: Once considered a staple of therapy, the role of radiation therapy in borderline resectable pancreatic cancer is evolving as systemic therapy regimens continues to improve. Increased clinical understanding of disease phenotype and response are needed to accurately tailor therapy for individual patients and to improve outcomes in this complex patient population.

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades.

PURPOSE: When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion. METHODS AND MATERIALS: This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades. A literature review was performed to determine the publication outcomes of PRO data, including only trials that used PROs in their design and were mature enough to have published results. RESULTS: Fifty-seven (56.4%) of the 101 trials included in this study included PROs in their design. Brain and head and neck trials demonstrated the largest proportional incorporation of PROs (81.8% and 76.9%, respectively), and thoracic and breast trials used the fewest (18.8% and 37.5%, respectively). The EQ-5D family of questionnaires was the most commonly used PROs, used in 22.8% of trials included. The literature review demonstrated a pattern of increased publication of PRO data alongside survival endpoints in manuscripts derived from these trials over time. CONCLUSIONS: Though there is room for improvement, the field of radiation oncology has embraced the incorporation of PROs into multicenter, high-impact clinical trials over the past 2 decades and has increased its publication of this data alongside survival data from these trials.

The Radiation Oncology Education Collaborative Study Group 2020 Spring Symposium: Is Virtual the New Reality?

PURPOSE: Because of the COVID-19 pandemic, the Radiation Oncology Education Collaborative Study Group (ROECSG) hosted its annual international symposium using a virtual format in May 2020. This report details the experience of hosting a virtual meeting and presents attendee feedback on the platform. METHODS AND MATERIALS: The ROECSG symposium was hosted virtually on May 15, 2020. A postsymposium survey was distributed electronically to assess attendee demographics, participation, and experience. Attendee preference and experience were queried using 3-point and 5-point Likert-type scales, respectively. Symplur LLC was used to generate analytics for the conference hashtag (#ROECSG). RESULTS: The survey was distributed to all 286 registrants, with a response rate of 67% (191 responses). Seventeen nonattendee responses were omitted from this analysis, for a total of 174 included respondents. Eighty-two attendees (47%) were present for the entire symposium. A preference for a virtual symposium was expressed by 78 respondents (45%), whereas 44 (25%) had no preference and 52 (30%) preferred an in-person meeting. A total of 150 respondents (86%) rated the symposium as "extremely" well organized. Respondents who had not attended a prior in-person ROECSG symposium were more likely to prefer the virtual format (P = .03). Seventy-eight respondents (45%) reported a preference for the virtual platform for reviewing scholarly work, and 103 (59%) reported a preference for an in-person platform for networking. On the day of the symposium, #ROECSG had 408 tweets and 432,504 impressions. CONCLUSIONS: The 2020 ROECSG symposium was well received and can serve as a framework for future virtual meetings. Although the virtual setting may facilitate sharing research, networking aspects are more limited. Effort is needed to develop hybrid virtual and in-person meetings that meet the needs of participants in both settings. Social media is a significant avenue for dissemination and discussion of information and may be valuable in the virtual setting.

Prognostic implications of advancing nodal stage in anal cancer: evaluating AJCC 8 staging changes through an NCDB analysis.

PURPOSE: In the AJCC8, nodal staging for squamous cell carcinoma of the anus (SCCA) has been changed to a binary format (N0 or N+), and overall stage groups have been redefined. We evaluated the effect of AJCC8 nodal stage by T stage and hypothesized similar survival regardless of the extent of AJCC7-defined nodal involvement. METHODS: The National Cancer Database (NCDB) was used to identify patients' SCCA. Overall survival (OS) for each T stage within the AJCC7 was compared with increasing nodal stage, as well as for the new AJCC8 overall stage groups and subsets. RESULTS: There were 6738 patients analyzed. The 5-year OS by AJCC8 stage was I = 81%, IIA = 78%, IIB = 64%, IIIA = 69%, IIIB = 59%, IIIC = 57% (p < 0.0001). In AJCC8 IIIA (T1-2, N+), there was no difference in 5-year OS between T1N+ or T2N+ patients (70.3% vs 68.6%, p = 0.09). A significant survival difference was demonstrated between AJCC7 N1, N2, and N3 for patients with either T1 (p = 0.0047) or T2 (p = 0.0389) disease. In the AJCC 8 IIIC (T3-4, N+) group, there was no difference in 5-year OS between T3N+ and T4N+ (58% vs 55%, p = 0.81). There was no OS difference between AJCC7 N1-3 for either T3 (p = 0.19) or T4 (0.35) disease. CONCLUSION: For earlier T stages, advancing nodal stage per AJCC7 retains prognostic implications for OS. Survival in AJCC8 stage IIIA is heterogeneous and is largely driven by burden of nodal disease in patients with T1-2 disease.

Intensity-modulated radiotherapy improves survival and reduces treatment time in squamous cell carcinoma of the anus: A National Cancer Data Base study.

BACKGROUND: Chemoradiation with 5-fluorouracil and mitomycin remains the standard of care for squamous cell carcinoma (SCC) of the anal canal. A prolonged treatment time is associated with inferior disease-specific outcomes. Radiation Therapy Oncology Group trial 0529 demonstrated decreased toxicity and fewer treatment breaks with intensity-modulated radiotherapy (IMRT), but this has not been assessed in a randomized trial. Using data from the National Cancer Data Base (NCDB), this study evaluated the impact of IMRT on treatment time and survival in anal SCC. METHODS: The NCDB was used to identify patients with anal cancer from 2004 to 2013. The included patients were those with stage I to III squamous cell cancer of the anal canal who had received definitive chemoradiation by IMRT or 3-dimensional conformal radiation therapy (3DCRT). Statistical analyses were performed with logistic regression, Kaplan-Meier analysis, Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS: Of 6814 patients, 57.4% were treated with 3DCRT, whereas 42.6% received IMRT. Patients receiving IMRT had a reduced risk of a long treatment time in a multivariate analysis (P < .001). The 5-year overall survival (OS) rates with IMRT and 3DCRT were 80.8% and 78.9%, respectively (P = .0036). According to a propensity analysis, patients receiving IMRT had improved OS (P = .039) and a reduced risk of a long treatment time (P < .0001) in a multivariate analysis. CONCLUSIONS: IMRT use was associated with significantly reduced overall treatment time and improved survival in comparison with 3DCRT. It is important to note that NCDB data are not as robust as randomized data. However, these results further support the use of IMRT as part of sphincter-preserving therapy for the anal canal.